The commonly cultivated edible mushroom Agaricus bisporus contains agaritine (synonym: Beta-N-[Delta-L(+)-glutamy]-4-hydroxymethylphenylhydrazine), and its metabolites, 4-hydroxymethylphenylhydrazine and 4-(hydroxymethyl)benzenediazonium ion. We have shown in this laboratory that two compounds of these series, the N-acetyl derivative of 4-hydroxymethylphenylhydrazine given orally and the tetrafluoroborate form of 4-(hydroxymethyl)benzenediazonium ion administered orally and subcutaneously induced tumors of lungs, blood vessels, subcutis, skin and glandular stomach in mice. This present proposal will 1) analyze Agaricus bisporus samples for other hydrazines which have been postulated in the biosynthesis of agaritine; 2) determine the tumor-inducing ability of these chemicals as well as the mushroom itself by long-term feeding in mice; 3) quantify the presence of 4-(hydroxymethyl)benzenediazonium salts in a minimum of 25 samples of Agaricus bisporus purchased locally; 4) test our hypothesis that arenediazonium salts are ultimate carcinogens formed from arylhydrazines and arylhydrazides through examination of in vitro metabolism of arylhydrazines and an investigation of the covalent binding of arenediazonium salts to DNA and its deoxynucleosides; and 5) further investigate the tumor inducing ability of 4-(hydroxymethyl)benezenediazonium ion (as the sulfate salt) in the Swiss mouse by oral and subcutaneous chronic administration. Thsu far around 55 hydrazine derivatives, including several arylhydrazines, have been shown to be tumor-producing substances in animals. Positive results in these studies would point to the possibility that some human cancer could be caused by naturally occurring constituents of the human food supply. The estimated U.S. mushroom consumption (production plus imports) totaled approximately 360 million pounds in 1975.